| First Author | Condon KH | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 9 | Pages | 3799-814 |
| PubMed ID | 23447592 | Mgi Jnum | J:196065 |
| Mgi Id | MGI:5486513 | Doi | 10.1523/JNEUROSCI.1930-11.2013 |
| Citation | Condon KH, et al. (2013) The Angelman syndrome protein Ube3a/E6AP is required for Golgi acidification and surface protein sialylation. J Neurosci 33(9):3799-814 |
| abstractText | Angelman syndrome (AS) is a severe disorder of postnatal brain development caused by neuron-specific loss of the HECT (homologous to E6AP carboxy terminus) domain E3 ubiquitin ligase Ube3a/E6AP. The cellular role of Ube3a remains enigmatic despite recent descriptions of synaptic and behavioral deficits in AS mouse models. Although neuron-specific imprinting is thought to limit the disease to the brain, Ube3a is expressed ubiquitously, suggesting a broader role in cellular function. In the current study, we demonstrate a profound structural disruption and cisternal swelling of the Golgi apparatus (GA) in the cortex of AS (UBE3A(m-/p+)) mice. In Ube3a knockdown cell lines and UBE3A(m-/p+) cortical neurons, the GA is severely under-acidified, leading to osmotic swelling. Both in vitro and in vivo, the loss of Ube3a and corresponding elevated pH of the GA is associated with a marked reduction in protein sialylation, a process highly dependent on intralumenal Golgi pH. Altered ion homeostasis of the GA may provide a common cellular pathophysiology underlying the diverse plasticity and neurodevelopmental deficits associated with AS. |
